Project Summary Progress in elucidating the role of the environment in child development and disability has been slow and incremental. Nearly all studies have examined relatively small populations of children; considered only one parameter at a time; had little power to examine interactions among chemical, social, and behavioral factors; had limited ability to examine gene?environment interactions; and suffered from brief duration of follow-up. NYU School of Medicine and Erasmus University Medical Center, in partnerships with multiple other institutions, respond to RFA-16-OD-004, presenting four cohorts for inclusion in the Environmental Influences on Child Health Outcomes Program (ECHO). These cohorts are the NYU Children's Environmental Health Study (n~1000, 2016?2018 births, NYU CHES); the Rotterdam-based Generation R Second Cohort (n~1000, 2016?2018 births, GR2); the First Generation R Study (n=1431, 2004?2006 births, GR1); and the Infant Development and Environment Study II (n=717, 2010?2012 births, TIDES). Together, they would comprise ~9% of all human subjects within ECHO. All four cohorts are well suited to examination of perinatal outcomes; upper and lower airway; and neurodevelopment, and offer substantial flexibility in prospective collection and the use of existing biospecimens. Though our proposed aims focus on chemical exposures, our cohorts also take a broad approach to biological, psychosocial, and physical exposures, which are equally influential on health outcomes. GR1 is widely known as a model for ECHO, given its track record of successful implementation, much like Project Viva. Moreover, GR1 measures could be used to evaluate the promise and feasibility of common ECHO exposures and outcome measures for use in more recently established cohorts. First-trimester recruitment and collection of urine samples in each trimester are common to all four cohorts. A unique benefit to inclusion of GR2 is its nesting within Rotterdam's municipal preconception care program, permitting examination of preconceptional exposures (generally unavailable in US cohorts). GR1's unique abdominal MRI, pulse wave velocity, and echocardiographic measures permit studies of end-organ effects. ECHO funding would extend NYU CHES and GR2 through age 2 years, GR1 through age 13 years, and TIDES through age 9 years, examining prenatal exposures in relation to early life trajectories of body mass. The proposed NYU-Erasmus ECHO Pediatric Obesity, Metabolism and Kidney Cohort Center pairs an internationally known leader in children's environmental health (Trasande) with a leader in the Developmental Origins of Health and Disease (Jaddoe) as multiple PIs and leverages extensive expertise in fetal growth, epidemiology, biostatistics, metabolomics, epigenetics among other disciplines that contribute to high-quality execution of synthetic cohort studies, and guide prevention.